Light is the only electromagnetic wave known to be sensitive to molecular conformation, and as such is an essential tool for probing the structure and properties of matter and for monitoring physical, chemical or biological processes. Light, as opposed to potentially harmful X-rays, is an ideal non-ionizing radiation for imaging and treating biological tissues. Despite the advantages of light as a means of probing and monitoring structures and processes, the application of light imaging techniques such as optical imaging is limited within biological tissues and other heterogeneous media.
Optical imaging through a highly scattering medium, such as biological tissue, has been stymied by the loss of optical focusing due to the effects of optical scattering due to refractive index variations within the medium. Current optical imaging techniques, such as optical coherence tomography, are limited to a depth of approximately one optical transport mean free path, typically about 1 millimeter within biological tissues. Other well-known techniques, such as confocal microscopy and multi-photon microscopy, have even more restricted penetration paths. Other imaging techniques, such as diffuse optical tomography or thermal wave microscopy, have relatively low depth to resolution ratios.
Accordingly, focusing light into a scattering medium is much more valuable than focusing through the scattering medium. In fact, the former can be reduced to the latter by moving the ultrasound focus. Focusing through a scattering medium may be used to image a target outside a scattering medium, which can be either viewed directly from the target side or scanned by a collimated laser beam. Focusing light into the scattering medium must be used to image or treat a target embedded within a scattering medium. For example, when a tumor inside biological tissue is optically imaged or treated, light must be focused to the tumor.
High-resolution optical imaging relies on the ability to focus light precisely into a scattering medium at a desired depth. Photodynamic therapy and optogenetics also make use of light focused and/or delivered to specific regions of interest inside biological tissue. However, multiple scattering bodies such as cells, tissues, and organs within scattering media such as biological tissues impose a fundamental optical diffusion limit on direct light focusing in scattering media. Consequently, the imaging depth of current forms of focusing optical microscopy, such as confocal microscopy, may be limited to less than one transport mean free path. A number of technologies have been developed that attempt to address this limitation. For example, light can be focused through biological tissue by optical phase conjugation, or focused into a static scattering medium by iterative wavefront shaping, which maximizes the signal strength of a blurred yet visible implanted target in a scattering medium.
Time-reversed ultrasonically encoded (TRUE) optical focusing is a recently-developed technique that may be used to illuminate a scattering medium with a coherent light source. The TRUE optical focusing technique is described in detail in pending U.S. Non-Provisional application Ser. No. 13/574,994, which is hereby incorporated by reference in its entirety. In brief, diffused coherent light introduced into a scattering medium may be encoded by a focused ultrasonic wave acting as an internal “guide star” inside the scattering medium. Only the encoded light emerging from the guide star is time-reversed and transmitted back, thereby providing illumination to the guide star region within the scattering medium. At present, the TRUE optical focusing technique is limited to focusing light to the discrete guide star region, and the light must pass through the scattering medium. As a result, a significant portion of the coherent light introduced into the scattering medium may be lost to scattering within the intervening scattering medium situated between the guide star, the coherent light source output, and the encoded light collecting optics.
A need exists for an enhanced method of focusing light into a scattering medium, such as biological tissue, that is tolerant of dynamic microstructures. In particular, there is a need for an enhanced system and method of penetrating and focusing light beyond the optical transport mean free path within a scattering medium.